The formation of bile that contains more cholesterol than can be solubilized by the bile acid and phospholipid content of that bile leads to precipitation of cholesterol crystals and formation of cholesterol gallstones. Chenodeoxycholic acid (CDC) reverses this biliary lipid defect and dissolves gallstones. Insufficient data is available, however, on factors that influence the efficacy and safety of chenodeoxycholic acid in gallstone dissolution and on its mechanism of action. Furthermore, other potential agents for gallstone dissolution have not been fully explored. The overall objectives of this proposal are to study the pathogenesis of cholelithiasis and factors influencing the efficacy, safety and mechanism of action of CDC and to evaluate other potential agents for the dissolution of gallstones. Methods include determinations of biliary bile acids, lecithin and cholesterol and of hepatic lipids, morphology and activities of HMG-CoA reductase and 7 alpha hydroxylase. Further studies will be conducted in a hamster model developed to assess the hepatic and biliary lipid effects of agents that may be useful for gallstone dissolution in man. In particular, the influence of dietary cholesterol, hormones and drugs such as phenobarbital and estrogens on the effects of CDC will be determined.